WO2006032847A1 - Guérison de blessures - Google Patents

Guérison de blessures Download PDF

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Publication number
WO2006032847A1
WO2006032847A1 PCT/GB2005/003536 GB2005003536W WO2006032847A1 WO 2006032847 A1 WO2006032847 A1 WO 2006032847A1 GB 2005003536 W GB2005003536 W GB 2005003536W WO 2006032847 A1 WO2006032847 A1 WO 2006032847A1
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WO
WIPO (PCT)
Prior art keywords
wound healing
formula
compound
wound
wounds
Prior art date
Application number
PCT/GB2005/003536
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English (en)
Inventor
Stanley Beames Brown
Cassandra Clare O'grady
Original Assignee
Photopharmica Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Photopharmica Limited filed Critical Photopharmica Limited
Priority to DE602005024590T priority Critical patent/DE602005024590D1/de
Priority to DK05782564.8T priority patent/DK1797053T3/da
Priority to JP2007531821A priority patent/JP5118967B2/ja
Priority to AT05782564T priority patent/ATE486860T1/de
Priority to EP05782564A priority patent/EP1797053B1/fr
Publication of WO2006032847A1 publication Critical patent/WO2006032847A1/fr
Priority to US11/723,523 priority patent/US7407953B2/en
Priority to US12/176,782 priority patent/US20090023715A1/en
Priority to US12/899,365 priority patent/US20110028459A1/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B5/00—Dyes with an anthracene nucleus condensed with one or more heterocyclic rings with or without carbocyclic rings
    • C09B5/24—Dyes with an anthracene nucleus condensed with one or more heterocyclic rings with or without carbocyclic rings the heterocyclic rings being only condensed with an anthraquinone nucleus in 1-2 or 2-3 position
    • C09B5/44—Azines of the anthracene series
    • C09B5/60—Thiazines; Oxazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
    • C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
    • C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
    • C07D279/18—[b, e]-condensed with two six-membered rings
    • C07D279/22—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom
    • C07D279/24—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom with hydrocarbon radicals, substituted by amino radicals, attached to the ring nitrogen atom
    • C07D279/28—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom with hydrocarbon radicals, substituted by amino radicals, attached to the ring nitrogen atom with other substituents attached to the ring system

Definitions

  • This invention relates to wound healing, the use of certain heterocyclic compounds and compositions and medicaments containing them in a wound healing process and for cosmetic uses.
  • the rate of chronic and acute wound healing can be delayed or impaired by a number of factors (exogenous and endogenous) and a variety of medical conditions. Examples include infection, ulceration particularly through diabetes, circulation problems associated with vascular disease, malnutrition, stress, cancer radiotherapy and/or chemotherapy, compromise of the immune system or simply due to the normal aging process. At present there is a clear need for therapeutic and cosmetic approaches that promote wound healing processes.
  • a phenothiazinium compound of Formula (1) for use in promoting wound healing in which the phenothiazinium compound is of Formula (1):
  • R 1 - R 6 each independently is selected from H, optionally substituted Ci- ⁇ - alkyl, F, Cl, Br and I;
  • a and B each independently is selected from:
  • Q is selected from H and optionally substituted C-i -8 -alkyl
  • Z is selected from C(R a ) 2 , O 1 S, SO 2 , NR a in which each R a independently is selected from H and optionally substituted C-i- ⁇ -alkyl;
  • R 7 and R 8 each independently is selected from H and optionally substituted C 1-8 -alkyl
  • Y is a counteranion; and p is 1 , 2 or 3.
  • R 1 - R 8 , R a or Q is optionally substituted alkyl
  • the optional substituents are preferably selected from aryl, particularly Ph; F; Cl; Br; I; OH; OC 1-4 -alkyl, particularly OCH 3 , OC 2 H 5 , OC 3 H 7 ; CN; OCOC- M -alkyl, particularly OCOCH 3 ; optionally substituted C 3-6 -cycloalkyl, particularly cyclohexyl, methyl-substituted cyclohexyl, cyclopentyl, and methyl- substituted cyclopentyl; COOH; COOCi -4 -alkyl; SO 3 H;
  • the alkyl groups represented by R 1 - R 8 , R a or Q may be straight or branched chain and may optionally include C-C double or triple bonds.
  • R 1 - R 6 each independently is preferably selected from H, CH 3 , F, Cl, Br and
  • a and B are both NR 7 R 8 , R 7 and R 8 each independently preferably is selected from H and Ci -6 -alkyl optionally substituted by Ph, F, Cl, Br, I, OH, OCH 3 , OC 2 H 5 , OC 3 H 7 , CN, OCOCH 3, cyclohexyl, methyl-substituted cyclohexyl, cyclopentyl, and methyl-substituted cyclopentyl.
  • Q is preferably H or CH 3 .
  • Z is preferably selected from CH 2 , O, S, SO 2 , NH, NCH 3 , NC 2 H 5 ,
  • R a is preferably selected from H, CH 3 , C 2 H 5 , CH 2 CH 2 OH and COCH 3 .
  • Y may be an organic or inorganic counteranion is preferably selected from F ' , Br ' , Cl “ , I “ , NO 3 “ , SON " , CIO 3 “ , CIO 4 “ , 1O 3 “ , BF 4 " , HSO 4 " , H 2 PO 4 -, CH 3 SO 4 " , N 3 " , SO 4 2” , HPO 4 2” , PO 4 3” , acetate, lactate, citrate, tartrate, glycolate, glycerate, glutamate, ⁇ -hydroxyglutamate, glucouronate, gluconate, malate and aspartate.
  • R 7 and R 8 together with the nitrogen atom to which they are attached may form an optionally substituted 5-, 6- or 7-membered ring.
  • the rings formed from one or both of R 7 and R 8 together with the nitrogen atom to which they are attached and from the groups R 1 and R 2 and/or R 4 and R 5 together with the carbon atoms to which they are attached may be saturated or unsaturated.
  • the optional substituents for the optionally substituted 5-, 6- or 7-membered rings formed from R 7 and R 8 together with the nitrogen atom to which they are attached, and formed from the groups R 1 and R 2 and/or R 4 and R 5 together with the carbon atoms to which they are attached may be selected from any of those substituents described above for R 1 .
  • methylene blue and ring substituted derivatives thereof and toluidine blue are excluded from the compounds of Formula (1).
  • a compound of Formula (1) for use as a wound healing agent is provided.
  • a wound healing agent comprising a compound of Formula (1) and a pharmaceutically acceptable diluent or excipient.
  • the present invention also provides a composition, preferably a pharmaceutical composition, for use in promoting wound healing that comprises a phenothiazinium compound of Formula (1) together with a diluent or excipient.
  • a use of a compound according to Formula (1) in the manufacture of a medicament for promoting wound healing may be in a form for topical or systemic use and is preferably in a form for topical use.
  • the medicaments are preferably administered topically more preferably administered as a cream, suspension, emulsion, gel, ointment, salve, stick, soap, paste, or via an antimicrobial dressing such as a bandage impregnated with a compound of Formula (1) or a composition or medicament comprising a compound of Formula (1).
  • the wound healing agents, compositions and medicaments provided by the present invention may comprise mixtures of two or more different compounds of Formula (1); they may also further comprise one or more different therapeutic or active agents.
  • a method for promoting wound healing in both chronic and acute wounds by applying or administering a phenothiazinium compound of Formula (1) to a wound site, and optionally exposing the wound site to light. More specifically the method for promoting wound healing includes the following steps: a) preparing a composition or medicament comprising a compound of Formula (1); b) applying or administering an effective amount of the composition or medicament to a wound area to be treated: and c) optionally exposing the wound area to light.
  • the compounds, compositions, wound healing agents and medicaments of the present invention may be used to treat any condition where the integrity of tissue is damaged, and thus covers chronic and acute wounds, wounds in connective tissue and wounds in muscle, bone and nerve tissue.
  • the wounds may include, but are not limited to the following: surgical wounds; bites; burns; acid and alkali burns; cold burn (frostbite), sun burn, minor cuts, major cuts, abrasions, lacerations, wounds caused by gunshot or knife injury; wounds caused by congenital disorders; wounds following dental surgery; periodontal disease; wounds following trauma; tumour associated wounds, which can be classified as malignant cutaneous ulcers related to the primary tumour or metastases; ulcers, leg ulcers; foot ulcers; pressure sores and corneal wounds.
  • Wounds can be classified by having either an acute or chronic etiology.
  • Acute wounds are caused by external damage to intact skin and include surgical wounds, bites, burns, cuts and abrasions, as well as more traumatic wounds such as lacerations and those caused by crush or gun shot injuries.
  • Chronic wounds are most frequently caused by endogenous mechanisms associated with a predisposing condition that ultimately compromises the integrity of dermal or epithelial tissue.
  • Pathophysiological abnormalities that may dispose to the formation of chronic wounds such as leg ulcers, foot ulcers, and pressure sores include compromised tissue perfusion as a consequence of impaired arterial supply (peripheral vascular disease) or impaired venous drainage (venous hypertension) and diseases such as diabetes mellitus.
  • AIDS AIDS
  • drugs e.g. chemotherapy or radiation therapy
  • chronic ulceration e.g. pressure or decubitis ulcers have a different etiology from other chronic wounds in that they are caused by sustained external skin pressure, most commonly in the buttocks, sacrum, and heels. All chronic wounds heal slowly and in an unpredictable manner (Bowler, et al, Clinical Microbiology Reviews, 14 (2) 244). For example, in a study of diabetic foot ulcers, with 20 weeks of good wound care only 31 % of the ulcers healed (Margolis, et al. Diabetes Care, 22 (5), 692).
  • the present compounds, compositions, wound healing agents and medicaments, and method for promoting wound healing may be used any time from wound identification to treat chronic and acute wounds, for wounds that are treated surgically such times include pre-, during or post surgery, prior to surgical repair, and post surgical repair, to aid wound healing, preferably at a time from 0 to 7 days after, more preferably from 2 to 6 days after applying or administering the compound of Formula (1).
  • the area to be treated is optionally exposed to light, and where exposed to light the time between application or administration of the compound and exposure to light is as defined below.
  • tissue welding tissue welding
  • tissue grafting including grafting used in transplant surgery.
  • They may be used to heal inflammatory disorders of the skin that result in itching, crusting, scaling or blisters, such as eczema, psoriasis and acne.
  • the method invention may also be used to treat forms of eczema that are weakened by the immune response (allergy) such as atopic dermatitis.
  • compositions, wound healing agents and medicaments may need to be repeated and typically from 1 to 20 treatments may be applied, more preferably from 1 to 5 treatments to promote wound healing.
  • the compounds, compositions, wound healing agents, medicaments and methods described herein are preferably used for treating epithelial wounds, more preferably for treating skin wounds.
  • a cosmetic agent for example for uses in skin rejuvenation and thickening, reducing scar formation and birth mark removal.
  • a method that may be used for cosmetic purposes, including, but not limited to, skin rejuvenation and thickening, reducing scar formation and birth mark removal.
  • the cosmetic method includes the following steps: a) preparing a composition comprising a compound of Formula (1); b) applying or administering an effective amount of the composition to an area to be treated: and c) optionally exposing the wound area to light.
  • the wound is an internal wound, such as a stomach ulcer
  • the compound, composition, wound healing agent or medicament may be applied via an endoscope and where it is desirable to expose the wound site to light this may be achieved by use of an endoscopic light source.
  • the compound of Formula (1) may be applied directly to the wound site or in a pharmaceutically acceptable composition, wound healing agent or medicament.
  • the compound, composition, wound healing agent or medicament may be administered locally or topically and delivered via a variety of means, for example via a spray, local injection, local infusion, cream, lotion, suspension, emulsion, gel, ointment, salve, stick, soap, liquid aerosol, powder aerosol, drops, paste, endoscopically or antimicrobial dressings such as bandages.
  • administration is topical, more preferably as a cream, suspension, emulsion, gel, ointment, salve, stick, soap, paste, or via an antimicrobial dressing, and especially as a cream, suspension, emulsion, gel or ointment.
  • the compounds of Formula (1) may be formulated into a variety of pharmaceutical compositions, wound healing agents or medicaments which contain the compounds and pharmaceutically acceptable carriers, excipients, adjuvants (each selected for certain characteristics that permit optimal formulation); these may include liposomes, nanoparticles, colloidal suspensions, micelles, microemulsions, vesicles and nanospheres.
  • compositions, wound healing agents or medicaments may also comprise further components such as conventional delivery vehicles and excipients including organic liquids such as alcohols (for example ethanol, propanol and isopropanol), dimethyl sulphoxide, glycols such as propylene glycol and polyethylene glycol, liquid, semi-solid and solid paraffins, water, saline, solubilisers such as castor oil derivatives for example ethoxylated castor oils like Cremophor EL (trade mark BASF AG) or Tween (trade mark, ICI Americas Inc.) types, Unguentum (trade mark, Merck KGaA), Solutol (trade mark, BASF AG), isotonising agents such as urea, glycerol, aminoethanol, propylene glycol, pH regulators, dyes, gelling agents, thickeners, buffers, hydrocarbon waxes and combinations thereof.
  • organic liquids such as alcohols (for example ethanol, propanol and isopropanol),
  • compositions, wound healing agents or medicaments may further comprise a mild reducing agent for example a sugar such as glucose or dextrose; ascorbic acid; sodium metabisulphite and nicotinamide adenine dinucleotide (NADH).
  • a mild reducing agent for example a sugar such as glucose or dextrose; ascorbic acid; sodium metabisulphite and nicotinamide adenine dinucleotide (NADH).
  • NADH nicotinamide adenine dinucleotide
  • the compositions, wound healing agents or medicaments are prepared by mixing a compound of Formula (1) with one or more pharmaceutically acceptable carriers at an appropriate temperature, typically from 15° to 4O 0 C at an appropriate pH, typically from pH 3 to 9 and preferably at a physiologically acceptable pH such as from pH 6.5 to 7.5.
  • concentration of the compounds of Formula (1) in the compositions, wound healing agents or medicaments depends on the compound's photosensitising ability and is typically in the range from
  • Dry compositions, wound healing agents or medicaments which may be reconstituted before use are also provided in the present invention. These may be prepared by dry mixing solid components or preparing a liquid composition which is evaporated to dryness generally under mild conditions under vacuum or in low temperature ovens, freeze drying is a suitable drying technique.
  • the compounds of Formula (1) may also be administered systemically by any convenient means, for example intravenously, orally, sub-cutaneously, intramuscularly, directly into affected tissues and organs or intraperitoneally. Application or administration by any of the means described above may need to be repeated and typically from 1 to 20 treatments may be applied, more preferably from 1 to 5 treatments to promote wound healing.
  • the dose rate of the compounds of Formula (1) for topical, direct or systemic administration is preferably in the range from 0.1 to 2000 ⁇ mol, preferably in the range 10 to 1000 ⁇ mol, more preferably from 50 to 500 ⁇ mol.
  • typical injections volumes are in the range 0.1 to 100ml, preferably from 5 to 50ml. Where wound healing is promoted on exposure to light the light is preferably at wavelengths of 600 - 800 nm, more preferably at wavelengths from 630 nm to 700 nm
  • the light source may be any appropriate light source such as light emitting diode (LED), a laser or laser diode, a broad spectrum halogen lamp, or filtered lamp.
  • the light dose administered during PDT can vary but preferably is from 1 to 200 J/cm 2 , more preferably from 5 to 100 J/cm 2 , especially from 5 to 75 and ideally from 5 to 25J/cm 2 .
  • Wound healing promotion may be achieved by applying or administering the drug alone or by applying or administering the drug and exposing to light. Generally, where light exposure is given this may be at the time of drug administration or up to 12 hours after drug administration and the time may be tailored according to the wound being treated, the method of drug delivery and the specific compound of Formula (I) used. Light exposure is preferably given at any time from the time of drug administration up to 3 hours, more preferably from the time of drug administration up to 1 hour. Where the phenothiazinium compound is administered topically the wound is preferably left occluded in the dark for up to 1 hour, more preferably from 1 to 20 minutes, and especially from 8 to 12 minutes before exposure to light. Increasing the intensity (fluence rate) of the light dose generally reduces light exposure times. It is preferred that exposure to light is localised to the area/region to be treated, and where wounds are being treated more preferably localised to the wound itself.
  • the compounds of Formula (1) and compositions, wound healing agents and medicaments comprising compounds of Formula (1) may be used in the dark or on exposure to light to promote wound healing. In the dark it is the compound of Formula (1) alone that promotes wound healing.
  • phenothiazinium salts of Formula (1) may be synthesised as follows:
  • mice A study to investigate the effect of 3,7-bis(N,N-dibutylamino) phenothiazin-5- ium bromide PDT on wound healing in spontaneous diabetic mutation (strain c57BLKs/Bom db/db obtainable from Taconic, Denmark) mice Background
  • the delayed healing model is representative of a chronic wound, and wound healing effects of drugs can be more closely monitored and more easily measured.
  • mice 6 control non diabetic mice (db/+), 6 control diabetic (db/db) mice and 6 (db/db) PDT treated diabetic mice.
  • the wound was then covered and left for 6 minutes and 40 seconds. Following this, the wound was illuminated with 688nm light, at a fluence rate of 125mW/cm 2 to give a light dose of 25J/cm 2 .
  • Dressings were reapplied immediately after treatment and subsequently on post-wounding days 7 & 10.
  • Cybernetics, USA was used to calculate wound closure from wound images in each of the experimental groups over time. For each wound at each time point - open wound area was measured and expressed in terms of % wound area relative to day 4 (treatment day).
  • 3,7-bis(N,N-dibutylamino) phenothiazin-5-ium bromide provides a significant increase in the rate of wound healing when the control diabetic mice and treated diabetic mice are compared - 67% wound area remaining vs. 46% remaining respectively.
  • the treated diabetic mice showed a small increase in wound healing when compared with the control non diabetic mice - 46% wound area remaining vs. 48% remaining respectively.
  • the cream was rubbed into the ulcer so underlying skin/tissue could be seen through the cream. If this was not possible excess cream was removed.
  • the ulcer was then illuminated using a broad band CureLight (obtainable from PhotoCure) lamp at a fluence rate of 20-50 mW/cm 2 giving a total light dose of 50 J/cm 2 .
  • the ulcer area was measured pre treatment and after 1 week and one month. Results
  • Example 4 A study to investigate the effect of 10OuM and 50OuM 3,7-bis(N,N- dibutylamino) phenothiazin-5-ium bromide on wound healing in the Wistar rat
  • the wounds heal faster at a 500 ⁇ M concentration than at 100 ⁇ M.

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  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Diabetes (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Hematology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Rheumatology (AREA)
  • Surgery (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Obesity (AREA)
  • Cardiology (AREA)
  • Toxicology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Cosmetics (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention décrit un composé de type phénothiazinium, ainsi que des préparations et des médicaments employés dans le but d’améliorer la guérison de blessures. La présente invention a également pour objet une méthode permettant soit d'améliorer la guérison de blessures, soit d’améliorer une application de type cosmétique. Ladite méthode consiste en l’application ou l’administration d’un composé de type phénothiazinium sur une blessure ou sur la peau, et éventuellement en l’exposition de ladite blessure ou peau à la lumière.
PCT/GB2005/003536 2004-09-20 2005-09-14 Guérison de blessures WO2006032847A1 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
DE602005024590T DE602005024590D1 (de) 2004-09-20 2005-09-14 Phenothiazin-Derivat zur Wundheilung
DK05782564.8T DK1797053T3 (da) 2004-09-20 2005-09-14 Phenothiazinium-forbindelse til sårheling
JP2007531821A JP5118967B2 (ja) 2004-09-20 2005-09-14 創傷治療
AT05782564T ATE486860T1 (de) 2004-09-20 2005-09-14 Phenothiazin-derivat zur wundheilung
EP05782564A EP1797053B1 (fr) 2004-09-20 2005-09-14 Dérivé de phenothiazine pour guérison de blessures
US11/723,523 US7407953B2 (en) 2004-09-20 2007-03-20 Wound healing
US12/176,782 US20090023715A1 (en) 2004-09-20 2008-07-21 Wound Healing
US12/899,365 US20110028459A1 (en) 2004-09-20 2010-10-06 Wound Healing

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0420888A GB0420888D0 (en) 2004-09-20 2004-09-20 Compounds and uses
GB0420888.0 2004-09-20

Related Child Applications (1)

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US11/723,523 Continuation-In-Part US7407953B2 (en) 2004-09-20 2007-03-20 Wound healing

Publications (1)

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WO2006032847A1 true WO2006032847A1 (fr) 2006-03-30

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US (3) US7407953B2 (fr)
EP (1) EP1797053B1 (fr)
JP (1) JP5118967B2 (fr)
AT (1) ATE486860T1 (fr)
CY (1) CY1111177T1 (fr)
DE (1) DE602005024590D1 (fr)
DK (1) DK1797053T3 (fr)
ES (1) ES2358760T3 (fr)
GB (1) GB0420888D0 (fr)
PT (1) PT1797053E (fr)
WO (1) WO2006032847A1 (fr)

Cited By (21)

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WO2009137900A3 (fr) * 2008-05-12 2010-12-29 Fundação De Amparo À Pesquisa Do Estado De São Paulo - Fapesp Procédés de stabilisation de radicaux cationiques de composés phénothiaziniques, formulations cosméceutiques et méthode pour prévenir les maladies et problèmes cutanés
US7950396B2 (en) 2006-04-28 2011-05-31 Ondine International Holdings Ltd. Treatment for otitis externa
EP2365829A1 (fr) * 2008-11-07 2011-09-21 Klox Technologies Inc. Combinaison d un oxydant et d un photoactivateur destinée à la cicatrisation
US8227459B2 (en) * 2007-04-03 2012-07-24 Prosetta Antiviral Inc. Diamino-phenothiazinyl derivatives as antiviral treatments
US8685466B2 (en) 2009-07-17 2014-04-01 Klox Technologies Inc. Combination of an oxidant, a photosensitizer and a wound healing agent for oral disinfection and treatment of oral disease
US8759336B2 (en) 2011-03-17 2014-06-24 Prosetta Antiviral Inc. Antiviral compounds
US8785434B2 (en) 2010-04-30 2014-07-22 Prosetta Antiviral Inc. Antiviral compounds
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DK1797053T3 (da) 2011-02-21
JP5118967B2 (ja) 2013-01-16
US20110028459A1 (en) 2011-02-03
EP1797053A1 (fr) 2007-06-20
DE602005024590D1 (de) 2010-12-16
PT1797053E (pt) 2011-02-09
ES2358760T3 (es) 2011-05-13
US20070161625A1 (en) 2007-07-12
ATE486860T1 (de) 2010-11-15
US20090023715A1 (en) 2009-01-22
CY1111177T1 (el) 2015-06-11
US7407953B2 (en) 2008-08-05
JP2008513424A (ja) 2008-05-01
GB0420888D0 (en) 2004-10-20

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